Drug hypersensitivity involves the activation of T cells in an HLA allele–restricted manner. Because the majority of individuals who carry HLA risk alleles do not develop hypersensitivity, other parameters must control development of the drug-specific T cell response. Thus, we have used a T cell–priming assay and nitroso sulfamethoxazole (SMX-NO) as a model Ag to investigate the activation of specific TCR Vβ subtypes, the impact of programmed death -1 (PD-1), CTL-associated protein 4 (CTLA4), and T cell Ig and mucin domain protein-3 (TIM-3) coinhibitory signaling on activation of naive and memory T cells, and the ability of regulatory T cells (Tregs) to prevent responses. An expansion of the TCR repertoire was observed for nine Vβ subtypes, whereas spectratyping revealed that SMX-NO–specific T cell responses are controlled by public TCRs present in all individuals alongside private TCR repertoires specific to each individual. We proceeded to evaluate the extent to which the activation of these TCR Vβ–restricted Ag-specific T cell responses is governed by regulatory signals. Blockade of PD-L1/CTLA4 signaling dampened activation of SMX-NO–specific naive and memory T cells, whereas blockade of TIM-3 produced no effect. Programmed death-1, CTLA4, and TIM-3 displayed discrete expression profiles during drug-induced T cell activation, and expression of each receptor was enhanced on dividing T cells. Because these receptors are also expressed on Tregs, Treg-mediated suppression of SMX-NO–induced T cell activation was investigated. Tregs significantly dampened the priming of T cells. In conclusion, our findings demonstrate that distinct TCR Vβ subtypes, dysregulation of coinhibitory signaling pathways, and dysfunctional Tregs may influence predisposition to hypersensitivity.
The financial violation must be defined as a concept for the purpose of distinguishing this concept from other terms that may be suspected in the context of the job and the violations of the financial employee that may be disciplinary or even punitive. From Egypt and Iraq, in addition to addressing the doctrinal aspect in the two countries above and the extent to which the specialized jurists dealt with the statement of financial violations, or even highlighting images that could be considered that the violation committed by the financial employee falls under the framework of the financial violation. Which may result in a financial violation by the financial employee, and we touched upon the request of him to indicate the financial viola
... Show MoreThe study aims mainly to evaluate the performance of Sharq Dijila water treatment plant in removing turbidity for the period of 1-4-2001 to 31-3-2004. Daily data for turbidity of raw, clarified, filtered, and supplied water were analyzed. The results of the study showed that there is a wide variation in turbidity levels of raw water fluctuating between 10-1000 NTU with mean value of 41.3 NTU. Turbidity values of the clarified water varied between 1.4-77 NTU. Based on the turbidity value of 10 NTU and 20 NTU (the design maximum turbidity) the readings gave an acceptable percentage of 32.4% and 86% respectively. The turbidity of filtered water ranged between 0.2-4.5 NTU which are completely in compliance with Iraqi and WHO standards. In ac
... Show MoreIn this paper, we investigate the behavior of the bayes estimators, for the scale parameter of the Gompertz distribution under two different loss functions such as, the squared error loss function, the exponential loss function (proposed), based different double prior distributions represented as erlang with inverse levy prior, erlang with non-informative prior, inverse levy with non-informative prior and erlang with chi-square prior.
The simulation method was fulfilled to obtain the results, including the estimated values and the mean square error (MSE) for the scale parameter of the Gompertz distribution, for different cases for the scale parameter of the Gompertz distr
... Show Moreيمثل الأخذ بالنظام الفيدرالي أطاراً تنظيمياً لشكل الدولة و مرحلة تحول مهمة في بنية الدولة العامة في مختلف مجالاتها، فالانتقال من المركزية في أدارة الشؤون العامة للدولة الى النمط الفيدرالي يمثل تحولا بنيوياً وسيكولوجياً ،حيث يكون هنالك توزيع مكاني - عمودي للسلطة والثروة بين الوحدات المكونة للدولة بشكل يختلف كليا عن الحالة المركزية، ونجد صور تنظيمية عديدة تتأسس ضمن اطار الفيدرالية العام ،
... Show MoreIsmailism is of great importance in Islamic history and Islamic political thought. In different countries of the Muslim world today their presence exists and is active but is confused with mystery and secrecy. The most important characteristic of their political ideology is their dependence on the esoteric exegesis, which they have made an intellectual basis for which their most ideas relate, when they make for everything visible and exposed a hidden matter, not only aware of the esoteric exegesis, which only God knows and entrenched in science, and they mean imams or whoever They are called "(esoteric)" as a result of the Ismaili belief in esoteric interpretation and that everything is apparent inward, as well as they called the ((seven
... Show MoreThe water scarcity that Iraq suffers from and the low irrigation efficiency in irrigation projects, therefore, it was necessary to evaluate the performance of the irrigation system of the western canal for the Ishaqi irrigation project in Salah al-Din Governorate to determine the water management strategies that can be used to improve the irrigation efficiency in the project. The performance of the field irrigation system was evaluated on two fields of different crops and irrigation methods according to the agricultural reality of the study area in the Western canal for the Al-Ishaqi Irrigation Project in Salah Al-Din Governorate. The fieldwork included measurements of the moisture content before and after irrigation, fi
... Show MoreThe Egyptian labor movement is the oldest trade union movement in the Arab region. Beside, the labor movement in any society is, in fact, only a reflection of the extent of awareness of that class in that society. Such a comparison is based on the degree of social growth the working class has reached. Moreover, the Egyptian working class was characterized by modernity in its inception compared to other social forces and classes. In addition, its development is linked to the level of industrial development of the country. The peasants and craftsmen were the mainstay of production in the Egyptian society over several centuries. The labor union movement also represents the human aspect of the labor force when it encounters and interacts wit
... Show MoreMe researcher in this research study and discover the symbolic indications in the work of the Iraqi sculptor Morteza Haddad, has corrupted search of four chapters first chapter contains research problem and its significance and objectives of the research, which was to detect signs symbolism in works of contemporary Iraqi sculptor Morteza Haddad and terminology, which included significant the GTA and idiomatically and Velsfatta and conduct,
It also included the symbol for GTA and idiomatically and Velsfatta and hold, while the second chapter includes three sections are straight, semantics and icon, a brief on Iraqi contemporary sculpture, About the lives of contemporary Iraqi sculptor Then choose the terms of the research sample,
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